GENE EXPRESSION IN RESPONSE TO MECHANICAL LOADING ON THE ANTERIOR CRUCIATE LIGAMENT

Many tissues in the body, especially bone, have exhibited adaptive responses to lowmagnitude, high frequency mechanical loading. However, the response of ligament to these types of mechanical loads is not well understood. Therefore, the purpose of this study was to identify the mechanisms by which ligaments respond in vivo to high-frequency, low-magnitude mechanical loading by identifying (1) if there is a response to this mechanical loading, and (2) what genes are altered in response to this mechanical loading on the ligament. The left ACL of seven rabbits were subjected to in vivo, low-magnitude, high-frequency mechanical loading for twenty minutes, in a novel mechanical loading device, the RACL loader. Three rabbits served as external controls and received no loading. Following four hours to allow for genetic response, the ACL’s were harvested, and the RNA extracted to determine which genes were altered in expression in response to the loading. In response to mechanical loading, the loaded ACL had three genes differentially expressed compared to the internal control ACL. None of these three genes had annotations within the rabbit genome. The loaded ACL had 121 genes differentially regulated compared to the external control ACL (including 1 regulating collagen synthesis, and 15 with links to mechanotransductive pathways). This shows that there is a systemic response to mechanical loading in the ligament. Additionally, the genetic results shed light on the possible mechanotransduction response pathway in ligament. This study provides evidence that ligaments can be adapted through mechanical loading and may be used one day to strengthen a ligament for to reduce injury rates